Intro to pharm Flashcards
Antibacterial Agents
Bacitracin and gramicidin
Mupirocin
Polymyxin B sulfate
Neomycin and gentamicin
Topical antibiotics in acne: Clindamycin (Cleocin) Erythromycin (Erygel) Metronidazole (Metrogel) Sodium sulfacetamide
Topical Antiviral Agents
Acyclovir, penciclovir, docosanol (Abreva)
Topical antifungal preparations
Azoles – clotrimazole miconazole ketoconazole, Ciclopirox olamine Allylamines – terbinafine Butenafine Tolnaftate Nystatin and amphotericin B
Oral antifungal agents
Azoles – ketoconazole, itraconazole, fluconazole, voriconazole
Immunomodulators
Imiquimod
Tacrolimus and pimecrolimus
Acne Preparations
Retinoic acid and derivatives: retinoic acid (tretinoin), adapalene ,
tazarotene
Isotretinoin
Benzoyl peroxide
Drugs for Psoriasis
Acitretin
Tazarotene
Calcipotriene
Cyclosporine
Biologic response modifiers
TNF inhibitors – etanercept
infliximab , adalimumab
Anti-Inflammatory Agents
Topical corticosteroids
Examples include hydrocortisone, hydrocortisone valerate, triamcinolone acetonide, betamethasone
Keratolytic and Destructive Agents
Salicylic acid
Fluorouracil
Antipruritic Agents
Antihistamines
Trichogenic and Antitrichogenic Agents
Minoxidil , finasteride
Skin function:
Protection Thermal regulation Immune responsiveness Biochemical synthesis Sensory detection
Variables determining response
Drug penetration
Concentration gradient
Dosing schedule
Vehicles and occlusion
Drug Absorption
Three routes:
- Intact stratum corneum
- Sweat ducts
- Sebaceous follicles
Steps involved in percutaneous absorption:
- Concentration gradient established
- Partition coefficient
- Diffusion coefficient
Rate of absorption:
J = Cveh · Km · D/x
drying preparations to lubricating preparations
tinctures < wet dressings < lotions < gels < aerosols < powders < pastes < creams < ointments
what do we use for Chronic inflammation with xerosis, scaling, lichenification
creams and ointments
what do we use for Acute inflammation with oozing, vesiculation, and crusting
tinctures, wet dressings, and lotions
Transdermal Patches
fentanyl for pain lidocaine for neuralgia ethinyl estradiol/ norelgestromin for contraception nitroglycerin for angina scopolaine for motion sickness
general treatment approach for abrasions
clean minor injuries (scratches, cuts, abrasions) with soap and water
use of topical abx is mixed– worry about skin sensitivity/ promotion of resistance
clean wounds and remove debris
What are the mechanisms of action of the individual components of Neosporin (bacitracin, neomycin, polymyxin B)?
A. Increases permeability of cell wall
B. Inhibits cell wall synthesis
C. Inhibits 30S ribosomal subunit
polymixin B- increases permeability of cell wall
bacitracin- inhibits cell wall synthesis
neomycin- inhibits 30S ribosomal subunit
A 5 yo female is brought to urgent care by her mother after returning from kindergarten with red sores around her mouth.
You suspect non-bullous impetigo and would like to suggest a topical antibiotic ointment.
Which two topical antimicrobials cover group A β-hemolytic streptococci and S. aureus (including MRSA)?
Mupirocin
Neomycin
Polymyxin B
Retapamulin
neomycin and polymyxin B are not good for gram positive organisms.
Use mupirocin and retapamulin
mupirocin has good in vitro activity against MRSA but there’s no good clinical evidence
kid with non-bullous impetigo. General treatment approach
non-bullous impetigo- topical therapy with mupirocin or retapamulin for 5 days
more extensive forms of impetigo and bullous forms- oral abx for 7 days
Benefits of topical therapy: fewer side effects, lower risk of bacterial resistance.
Bacitracin-neomycin-polymixin B has some activity against impetigo causing organisms, but- may be less effective, and bacitracin and neomycin can cause contact dermatitis
Topical Antibiotics in Acne
Avoid systemic exposure and achieve high follicular concentrations
Less effective than systemic administration of the same antibiotic
Available options:
- Clindamycin
- Erythromycin
- Metronidazole
- Sodium sulfacetamide
Not used as monotherapy (bacterial resistance)!
- Give with benzoyl peroxide or retinoids
Clindamycin MOA
inhibits 50s ribosomal subunit
erythromycin MOA
inhibits 50s ribosomal subunnit
metronidazole MOA
damages DNA
sodium sulfacetamide MOA
inhibits folic acid synthesis
increased sebum production in acne creates a lipi rich microaerobic environment favorable to what organism?
propionibacterium acnes
A 35 yo male construction worker presents to his PCP with complaints of intense itching of both feet throughout the day.
PE: webs spaces white, macerated, cracked
Workup consistent with dermatophyte infection
What topical therapeutic options are available?
azoles, allylamine, butenafine, tolnaftate
pt/ provider preference, etc.
topical Azoles – clotrimazole, miconazole
MOA, uses
MOA: inhibits synthesis of ergosterol (inhibits lanosterol 14-α-demethylase)
Uses: tinea corporis (ring worm), tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea versicolor, and cutaneous candidiasis, such as vaginal yeast infections, infections of the skin, diaper rash, and thrush (candidiasis of the oral mucosa and tongue, and sometimes the palate, gingivae, and floor of the mouth)
topical Ciclopirox olamine
MOA, uses
MOA: inhibits uptake of precursors of macromolecule synthesis
Uses: topical dermatomycosis, candidiasis, tinea versicolor, mild-to-moderate onychomycosis
topical Allylamines – terbinafine and naftifine
MOA, uses
MOA: inhibits squalene epoxidase
Uses: tinea corporis, tinea cruris, and tinea pedis
topical tolnaftate MOA, uses
MOA unknown.
Uses: tinea pedis, tinea cruris, and tinea corporis
topical
Nystatin/amphotericin B
MOA, uses
MOA: binds ergosterol in fungal cell membrane altering permeability
Nystatin limited to topical cutaneous and mucosal uses
- Thrush
Amphotericin B broad antifungal spectrum but rarely used topically
Cumulative organ toxicity “ampho-terrible”
oral azoles: uses
Uses: vaginal, urinary, oropharyngeal, or esophageal candida infections
Systemic yeast infections more common: type 1 diabetes, leukemia, AIDS
Drug-drug interactions!
oral griseofulvin: MOA, uses
MOA: inhibits fungal cell mitosis at metaphase
Uses: dermatophyte infections but not Candida
Induces CYP enzymes
oral terbinafine: uses
High first pass metabolism; accumulates in skin, nails, fat
Uses: tinea corporis, tinea capitis, and onychomycosis
Antifungal Agents for dermatophyte infections- by location
Tinea capitis (scalp) – oral griseofulvin, terbinafine, itraconazole Tinea pedis (feet) – topical antifungals Tinea cruris (groin) – topical antifungals Tinea corporis (body) – topical antifungals, oral antifungals
antifungal agents for candida
Thrush (oropharyngeal candidiasis) – oral nystatin, clotrimazole troche, oral fluconazole
Esophageal candidiasis – systemic antifungals
Vulvovaginitis – topical antifungals, oral fluconazole
Invasive infection – systemic antifungals
A 40 yo male seeks your recommendation regarding frequent cold sores.
He experiences about ten cold sores a year, exacerbated by “colds” or sun exposure.
What organism is causing these cold sores?
He wants to know what treatment options are available to him.
Herpes simplex
topical acyclovir, penciclovir, or docosonol- modest benefit
apply within 1 hour of first sign or symptom, continue x 4 days
oral acyclovir, famcyclovir, valacyclovir- begin within 1 hour
chronic suppressive therapy for > 6 recurrences per year (acyclovir, valacyclovir)
Acyclovir, valacyclovir, penciclovir, famciclovir
MOA, uses
MOA: converted to pharmacologically active triphosphate metabolites, inhibit DNA synthesis and viral replication
Topical – modest benefit for herpes labialis
Systemic –
Most effective in treating herpes labialis
Also used systemically for HSV and VZV infections
Docosanol
MOA and uses
MOA: inhibits fusion between the plasma membrane and the HSV envelope, thereby preventing viral entry and replication
When applied within 12 hours of the onset of prodromal symptoms, five times daily, median healing time was shortened by 18 hours compared with placebo in recurrent orolabial herpes
Imiquimod
MOA, uses, ADRs
MOA: may be related to stimulation of peripheral mononuclear cells to release interferon-α and macrophage stimulation to produce interleukins-1, -6, -8, and TNF-α
Uses: external genital and perianal warts in adults, actinic keratoses on the face and scalp, biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities (< 2 cm diameter)
ADRs: local inflammation, pruritus, erythema, superficial erosion
Tacrolimus
MOA, uses, ADRs
MOA: inhibit T-lymphocyte activation and prevent release of inflammatory cytokines and mediators from mast cells
Uses: treatment of atopic dermatitis and psoriasis but traditionally used to prevent heart, liver, and kidney allograft rejection due to potent immunosuppressive activity (oral forms)
Topical ADRs: transient erythema, burning, and pruritus
What is the mechanism of action of benzoyl peroxide?
releases free-radical oxygen which oxidizes bacterial proteins, activity against P. acnes (no resistance)
14 y/o with mild acne. Other treatment options besides benzoyl peroxide?
topical retinoids: tretinoin (all-trans-retinoic acid)- also marketed as anti-aging
adapalene- photo-chemically more stable, less irritating
tazarotene– also approved for psoriasis, photoaging
MOA- may decrease cohesion between epidermal cells and increase epidermal cell turnover, expulsion of open comedones adn the transformation of closed comedones into open
ADRs: erythema, mild peeling and dryness; minimize sun exposure
CI: not recommended in pregnant women
Severe Cystic Acne- treatment
Isotretinoin (PO)
MOA: reduces sebacerous gland size, reduces sebum production
PK: t1/2 10-20 hours; hepatic metabolism; highly protein bound (99-100%)
ADRs: resemble hypervitaminosis A (dryness and itching)
Must pledge to be on 2 contraceptives and take pregnancy tests
Acne Treatment Approach
Comedonal (non-inflammatory) acne
- Topical retinoid
- Alternatives: azelaic acid, salicylic acid
Mild papulopustular and mixed acne
- Topical retinoid AND topical antimicrobial (BPO alone or BPO +/- topical antibiotic)
Moderate papulopustular and mixed acne
- Topical retinoid AND oral antibiotic AND topical BPO
Moderate nodular acne
- Topical retinoid AND oral antibiotic AND topical BPO
Severe nodular/conglobate acne
- Oral isotretinoin
Psoriasis topical therapy
Emollients – used as basic adjunct; reduces scaling, itching, and related discomfort
Keratolytics – reduce hyperkeratosis; enable other topical drugs to penetrate
Topical glucocorticoids – rapid response; control inflammation and itching; mainstay of topical treatment
2nd line alternatives:
Coal tar
Anthralin – used for widespread, refractory plaques
Calcipotriene – as effective as topical glucocorticoids but slower onset; no long-term glucocorticoid adverse effects
Tazarotene – extended response; maintenance therapy
Psoriasis systemic therapy
Used for patients with > 5% body surface area involvement
Methotrexate
- MOA: inhibits dihydrofolate reductase (folic acid analog)
- Used in combination with phototherapy or biological agents
- Effective for both skin lesions and arthritis
Acitretin
- Systemic retinoic acid derivative
- Not as effective as other systemic therapies
Cyclosporine
- MOA: inhibits calcineurin, inhibits transcription of interleukin-1 and -2 receptors, blocks T-cell activation
- ADRs: nephrotoxicity, hypertension, hepatotoxicity, gingival hyperplasia, and hirsutism
- Used in extensive disease in patients who are unresponsive to other agents
Psoriasis- Biologic Response Modifiers
Tumor necrosis factor inhibitors (etanercept, infliximab, adalimumab)
- MOA: prevents TNF mediated immune responses
- ADRs: risk of serious life-threatening infections (sepsis, pneumonia), exacerbation of congestive heart failure, and cause demyelinating disease in predisposed patients
- What infectious disease must be ruled out before initiating therapy with TNF inhibitors?
TB
Topical Corticosteroids
Immunosuppressive and anti-inflammatory
Local (topical & intralesional) or systemic (IM, IV, PO)
- Systemic therapy reserved for severe dermatological illness (allergic contact dermatitis to plants, life-threatening vesiculobullous dermatoses)
Corticosteroids are minimally absorbed following application to normal skin
Regional variation of percutaneous corticosteroid absorption
feet-- terrible palm forearm scalp- getting better forehead genitalia- most
Topical Corticosteroids
- groupings
Grouped into classes based on potency or approximate relative efficacy
Low to medium efficacy produce remission in disorders responsive to corticosteroids: seborrheic dermatitis, psoriasis of genitalia and face
High efficacy preparations useful in disorder less responsive to corticosteroids: psoriasis of palms and soles, sarcoidosis
ADRs: suppression of pituitary-adrenal axis
- Atrophy, steroid rosacea, steroid acne, allergic contact dermatitis
lowest to highest efficacy of topical corticosteroids
hydrocortisone betamethasone valerate hydrocortisone valerate betamehasone dipropionate Clobetasol propionate
Keratolytic Agents
Keratolytic: peeling agent causing softening/dissolution or peeling of stratum corneum
Salicylic acid
Uses: acne, seborrheic dermatitis, psoriasis, hyperkeratosis (corns, plantar warts, calluses); in combination with antifungal sodium thiosulfate for tinea versicolor
Salicylate toxicity can occur (nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, diarrhea, psychic disturbances)
AntiPruritic Agents
Corticosteroids, local anesthetics
Topical therapy useful in localized pruritus
Systemic therapy generally used for generalized pruritus
Antihistamines
First generation H1-receptor antagonists
- Diphenhydramine, promethazine
- Some anticholinergic activity, sedating, useful in nocturnal pruritus
Second generation H1-receptor antagonists
- Cetirizine, loratadine, desloratadine, fexofenadine
- Do no cross blood-brain barrier, lack anticholinergic side effects, non-sedatin
Trichogenic Agents
Trichogen: agent that promotes hair growth
Minoxidil
MOA: unknown
- Originally developed as an antihypertensive (PO dosing)
- Percutaneous absorption minimal but systemic effects on BP should be monitored in those with cardiac disease
Finasteride
- MOA: competitive and selective inhibitor of steroid 5α-reductase; blocks the conversion of testosterone to dihydrotestosterone (DHT)
- ADRs: decreased libido, ejaculation disorders, erectile dysfunction
- Pregnant women should not handle drug
